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RCI001作为原发性干燥综合征小鼠模型治疗候选药物的疗效

Efficacy of RCI001 as a Therapeutic Candidate in a Primary Sjögren Syndrome Mouse Model.

作者信息

Kang Hyereen, Jung Young-Ho, Moon Jayoon, Ryu Jin Suk, Yoon Chang Ho, Kim Yong Ho, Kim Mee Kum, Kim Dong Hyun

机构信息

RudaCure Co, Ltd, Incheon, Republic of Korea.

Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

Cornea. 2025 Feb 1;44(2):226-233. doi: 10.1097/ICO.0000000000003696. Epub 2024 Dec 26.

DOI:10.1097/ICO.0000000000003696
PMID:39288434
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11676593/
Abstract

PURPOSE

The aim of this study was to investigate the efficacy of RCI001 (RCI) in a mouse model of primary Sjögren syndrome.

METHODS

Eight 12-week-old NOD.B10-H2b mice were used in this study. All experimental animals were randomly divided into phosphate-buffered saline (PBS) and RCI groups in NOD.B10-H2b mice. The eyes of mice were topically treated with PBS or RCI twice a day for a week. Ocular surface staining (OSS) and tear secretion were compared between before and after treatment. The transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate oxidase (NOX) in the conjunctiva and cornea (CC) and lacrimal gland were assayed. In addition, immunofluorescence staining of the conjunctiva was assessed.

RESULTS

The RCI group showed significant clinical improvement in OSS and tear secretion after 1 week of treatment compared with the baseline (both P < 0.001) and showed better improvement in OSS and tear secretion than the PBS group after 1 week of treatment (both P < 0.05). The levels of IL-1β and IL-17 in CC and IL-6 in the lacrimal gland were also significantly reduced in the RCI group compared with the PBS group (each P < 0.05). Transcript levels of NOX2 and NOX4 were also significantly reduced in CC of the RCI group compared with those of the PBS group ( P < 0.05). The RCI group also resulted in lower conjunctival expression of oxidative stress markers (4-hydroxy-2-nonenal, hexanoyl-lysine, and NOX4) than the PBS group.

CONCLUSIONS

Topical RCI001 demonstrated excellent therapeutic efficacy in a mouse model of primary Sjögren syndrome by inhibiting inflammation and oxidative stress.

摘要

目的

本研究旨在探讨RCI001(RCI)在原发性干燥综合征小鼠模型中的疗效。

方法

本研究使用了8只12周龄的NOD.B10-H2b小鼠。所有实验动物在NOD.B10-H2b小鼠中随机分为磷酸盐缓冲盐水(PBS)组和RCI组。小鼠眼睛每天局部用PBS或RCI处理两次,持续一周。比较治疗前后的眼表染色(OSS)和泪液分泌情况。检测结膜和角膜(CC)以及泪腺中炎性细胞因子和烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX)的转录水平。此外,评估结膜的免疫荧光染色。

结果

与基线相比,RCI组在治疗1周后OSS和泪液分泌有显著临床改善(均P < 0.001),且在治疗1周后OSS和泪液分泌的改善程度优于PBS组(均P < 0.05)。与PBS组相比,RCI组CC中的IL-1β和IL-17水平以及泪腺中的IL-6水平也显著降低(各P < 0.05)。与PBS组相比,RCI组CC中NOX2和NOX4的转录水平也显著降低(P < 0.05)。RCI组结膜氧化应激标志物(4-羟基-2-壬烯醛、己酰赖氨酸和NOX4)的表达也低于PBS组。

结论

局部应用RCI001通过抑制炎症和氧化应激在原发性干燥综合征小鼠模型中显示出优异的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/fe1c3a53ef8f/cornea-44-226-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/5d2b0ca25065/cornea-44-226-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/c18cfcb272f1/cornea-44-226-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/ec01aa6d465a/cornea-44-226-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/e76bd44518de/cornea-44-226-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/fe1c3a53ef8f/cornea-44-226-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/5d2b0ca25065/cornea-44-226-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/c18cfcb272f1/cornea-44-226-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/ec01aa6d465a/cornea-44-226-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/e76bd44518de/cornea-44-226-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d76/11676593/fe1c3a53ef8f/cornea-44-226-g005.jpg

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本文引用的文献

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Front Med (Lausanne). 2023 Oct 9;10:1256569. doi: 10.3389/fmed.2023.1256569. eCollection 2023.
3
Comparison of Corneal Epithelial Wound Healing between Topical RCI001, Solcoseryl, and Polydeoxyribonucleotide in the Murine Ocular Alkali Burn Model.
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Korean J Ophthalmol. 2023 Jun;37(3):236-244. doi: 10.3341/kjo.2023.0019. Epub 2023 Jun 5.
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Oxidative Stress and Epigenetics: miRNA Involvement in Rare Autoimmune Diseases.氧化应激与表观遗传学:微小RNA在罕见自身免疫性疾病中的作用
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